ESTUDIO PATRICIA

As mentioned above, some organizations and many experts recommend that anal Pap tests and digital anal examination be part of the initial evaluation of both male and female HIV-infected patients. The intervals for screening have not been established, but (based on recommendations for cervical cancer screening) if the first test result is normal, the anal Pap usually is repeated in approximately 6 months. If both results are normal, then anal Pap tests can be performed annually. Some clinicians would consider more frequent screening in patients with genital warts, cervical dysplasia, or a history of treatment for anal dysplasia. Any patients with positive results should be referred for further evaluation; see below.

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kit. The swab or cytobrush should be inserted into the anal canal, past the anorectal junction, and withdrawn while rotating it against the anal walls to collect cells. The sample should then be handled according to the kit manufacturer’s instructions. (See “References,” below, for information about a video on how to conduct an anal Pap screen that is available from the Johns Hopkins University Local Performance Site of the Pennsylvania/MidAtlantic

AIDS Education and Training Center.) As with cervical cytology, anal cytology is graded using the Bethesda 2001 system, which categorizes disease in increasing order of severity as follows:

• Negative for intraepithelial lesion or malignancy • Atypical squamous cells of

undetermined significance (ASCUS) • Atypical squamous cells – cannot

exclude HSIL (ASC-H) • Low-grade squamous

intraepithelial lesion (LSIL) • High-grade squamous

intraepithelial lesion (HSIL) • Squamous cell carcinoma (SCC) Other abnormalities, such as atypical glandular cells (AGC), may be noted.

All individuals with abnormal anal cytology, defined as ASCUS or higher, should be referred for HRA and biopsy to grade the lesion. HRA typically is performed at specialty anal cancer practices or clinics, colorectal surgery and gastrointestinal specialty facilities, and some academic medical centers.

There currently are no recommendations concerning HPV testing of anal specimens. Evaluation of Cytologic Abnormalities HRA of the anal canal should be performed using a colposcope for magnification (16x) and the application of 3% acetic acid with or without Lugol iodine solution to aid in visualization of dysplastic lesions. Abnormal

areas should be examined by biopsy. Anoscopic features of high-grade disease are similar to those seen in the cervix; these include coarse punctation, mosaicism, and the presence of ring glands.

Treatment

The goal of treatment is to prevent progression to anal cancer. Treatment of HSIL to prevent anal cancer is biologically plausible, following the model of cervical dysplasia treatment. However, the indications for treatment of anal dysplasia, the efficacy of treatment, and the most effective treatments have not been optimally defined.

The focus of treatment is on high-grade, premalignant AIN. Patients should be referred to an anal dysplasia specialist specialty clinic, if possible. Specific treatment may vary depending on the size, location, extent of the lesions, and histological grade. Therapies include topical 5-fluorouracil, cryotherapy, infrared coagulation, laser therapy, and surgical excision. Infrared coagulation, an in-office procedure, has been shown to be effective in treating HIV-infected patients with high-grade dysplasia. With some

therapies, treatment-associated pain and other complications may occur, and recurrence of dysplastic lesions is common.

LSIL is not considered premalignant, but it frequently progresses to high-grade dysplasia. Some specialists do not treat LSIL but monitor regularly instead with HRA, whereas others choose to treat LSIL to prevent progression.

Prevention

Prevention of HPV infection can be challenging. Latex or plastic barriers may block transmission of HPV in areas covered by these barriers and their use is recommended to prevent transmission or acquisition of HPV (as well as HIV and other sexually transmitted diseases). However, infection may occur through bodily contact outside the area covered by the barriers.

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A quadrivalent HPV vaccine against certain oncogenic (types 16 and 18) and wart-

causing (types 6 and 11) types of HPV is FDA approved for prevention of anal dysplasia and anal cancer caused by the covered types in males and females 9-26 years of age, and for prevention of genital warts, its use is recommended. (The quadrivalent vaccine also is approved for prevention of cervical cancer and cervical, vaginal, and vulvar dysplasia). A second vaccine against HPV types 16 and 18 has been approved for females (see chapter Cervical Dysplasia).

The vaccine is not effective against HPV types other than those covered by the vaccine, and it may not be protective against a covered type to which a patient has been exposed previously. For optimal protection, the vaccine should be given before the individual is exposed to HPV through sexual activity. It is likely to be less effective in older adolescents and adults who may already have been infected with one or more of the covered HPV types. There are few data on the use of the vaccines in persons older than 26 years, and they are not approved for this group. Importantly, vaccination does not offer perfect protection from all oncogenic HPV viruses, so consideration should be given to screening individuals who have been vaccinated in the same way as unvaccinated individuals, as described above.

Patient Education

• All HIV-infected men and women should be encouraged to use condoms during vaginal, anal, and oral sex to prevent the spread of HPV. However, condoms do not offer complete protection from HPV.

• All patients should be counseled on how to reduce or avoid unprotected anal receptive intercourse.

• Both women and men who are HIV infected have an increased risk of developing anal dysplasia and cancer. MSM are at higher risk than other men of developing anal dysplasia. • Emphasize the importance of keeping

follow-up appointments to allow for early detection of precancerous lesions, further grading of abnormalities by HRA, and appropriate monitoring and treatment of abnormalities.

• Patients who have anal dysplasia should be informed about anal cancer symptoms, such as new-onset anal pain, bleeding, or the development of a mass. Patients should call their health care provider if these symptoms develop.

• If an anal Pap test is to be performed, advise patients to avoid having anal sex, douching, or using enemas before the test.

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References

• Aberg JA, Gallant JE, Ghanem KG et al.; HIV Medicine Association of the Infectious Diseases Society of America. Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jan;58(1):e1-e34.

• Chiao EY, Giordano TP, Palefsky JM, et al. Screening HIV-infected individuals for anal cancer precursor lesions: a systematic review. Clin Infect Dis. 2006 Jul 15;43(2):223-33. • Chin-Hong PV, Palefsky JM. Natural history

and clinical management of anal human papillomavirus disease in men and women infected with human immunodeficiency virus. Clin Infect Dis. 2002 Nov 1;35(9):1127-34. • Diamond C, Taylor TH, Aboumrad T, et al.

Increased incidence of squamous cell anal cancer among men with AIDS in the era of highly active antiretroviral therapy. Sex Transm Dis. 2005 May;32(5):314-20. • Hessol NA, Holly EA, Efird JT, et al. Anal

Intraepithelial neoplasia in a multisite study of HIV-infected and high-risk HIV-uninfected women. AIDS. 2009 Jan 2;23(1):59-70. • Massad LS, Einstein MH, Huh WK, et

al.; 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis. 2013 Apr;17(5 Suppl 1):S1-S27.

• Palefsky JM, Holly EA, Efirdc JT, et al. Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV- positive men who have sex with men. AIDS. 2005 Sep 2;19(13):1407-14.

• Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at aidsinfo.nih.gov/guidelines. Accessed December 1, 2013.

• Piketty C, Darragh TM, Da Costa M, et al. High prevalence of anal human papillomavirus infection and anal cancer precursors among HIV-infected persons in the absence of anal intercourse. Ann Intern Med. 2003 Mar 18;138(6):453-9.

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• A video titled Anal Pap Smear: A Simple, Fast and Easy Procedure is available on CD-ROM at-cost to health care professionals ($12.00 for 1-4 copies) by calling the Johns Hopkins University Local Performance Site of the Pennsylvania Mid/Atlantic AIDS Education and Training Center to order: 888-333-2855 (toll free) or by downloading the order form on the AETC NRC website. Available at aidsetc.org/aetc?page=etres- display&resource=etres-229. Accessed December 1, 2013.

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